6/30/16 1 + Update on the diagnosis, treatment, and prevention of feline upper respiratory tract infections Jessica Pritchard, VMD, DACVIM (SAIM) Clinical Instructor, SAIM, UW-Madison SVM + Feline Upper Airway Disease ! Etiologic agents, pathogenesis, clinical signs ! Viruses ! Chlamydophila felis ! Bordetella bronchiseptica ! Mycoplasma spp. ! Diagnostic tests and interpretation ! Therapeutic options ! Prevention Viruses, bacteria, and the path to chronic rhinitis + Etiologic agents, pathogenesis & clinical signs Viruses, bacteria and the path to chronic rhinitis + Etiology of nasal disease in 77 cats Neoplasia Chronic rhinitis Foreign body N-P stenosis Actinomyces Nasal Polyp Stenotic nares Trauma 27 30 8 5 2 2 2 1 Adapted from: Henderson, SM et al. Investigation of nasal disease in the cat – a retrospective study of 77 cases. JFMS (2004) 6, 245-257 + Viruses ! Feline herpesvirus-1 ! Feline calicivirus ! Influenza ! H5N1 (2006) ! H1N1 (2010) + Feline Herpesvirus ! Agent of feline viral rhinotracheitis ! Replicates in epithelial cells of conjunctiva, URT, neurons ! Neuronal infection leads to lifelong latency ! Susceptible to most commercially available disinfectants ! Shedding in oronasal and conjunctival secretions ! Environment is rarely the source of infection (catteries) ! Typically spread from cat to cat
12
Embed
ISVMA Feline URTD 2016Superficial and deep corneal ulcers (dendritic ulcers) Sneezing Nasal discharge Conjunctival hyperemia ... congestion and general malaise, as well as lip smacking
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
6/30/16&
1&
+
Update on the diagnosis, treatment, and prevention of feline upper respiratory tract infections
! Mycoplasma require special culture considerations
! Virus isolation ! Requires special media and handling
! False negatives due to viral numbers and fragility of organisms
! False positives given ability to culture these organisms from cats without clinical signs as well
+Viral PCR
! Detection of organism DNA
! Often available for FHV-1, FCV, C. felis, B. bronchiseptica, M. felis ! IDEXX Feline URD PCR Panel
! Swabs submitted from conjunctiva, oropharynx, nose
! Sensitivity issues
Respiratory pathogen panels
+Sites to submit for PCR testing
! 104 cats with signs of URTD
! Swabs submitted from nose, pharynx, tongue, conjunctiva
! PCR for FHV, Calici (FCV), C. felis
! 90% positive for one or more organisms ! 56% FHV-1 ! 50% FCV ! 35.6% C. felis
+Sites to submit for PCR testing
! 18 shelter cats with signs of URTD
! Compared PCR to VI and bacterial culture
! FHV-1 most common, FCV and C. felis least common
! Oropharyngeal swab with either conjunctival or nasal swab detected all organisms in each cat
The Veterinary Journal (In Press)
6/30/16&
6&
+Sites to submit for PCR testing
! FCV was found more frequently in the oropharynx and on the tongue (90.4%) than conjunctiva
! No significant difference between the four sampling sites for the detection of FHV-1 and C felis
! If only one site can be sampled, use the oropharynx ! Sampling multiple sites greatly increases chance of a positive
result
! If nasal samples had also been taken, 94.9% of FHV-1-positive cats, 96.2% of FCV-positive cats and 81.1% of C felis-positive cats would have been detected
+Advanced diagnostics
! Imaging ! Radiographs less sensitive
than CT
+Advanced diagnostics
! Retroflex pharyngeal evaluation and rhinoscopy
! Biopsy (blind versus scope-guided) ! Histopathology and brush
+Treatment Things you’re already doing , some things you haven’t tried yet, and a few you may try in the future
6/30/16&
7&
+General symptomatic treatment
Adapted from: Horzinek, MC. et al. Update on the 2009 guidelines of prevention and management of feline infectious diseases. JFMS (2013) 15: 530-539.
+General symptomatic treatment
! Nebulize/humidify
! Appetite stimulants ! Mirtazipine
! Nasal drops ! Phenylephrine
! Saline
+Antihistamines
! Lots of options, some may help for chronic rhinitis alone or in combination with other medications
Drug Dosage
Amitriptyline 5–10 mg/cat PO q12–24h
Chlorpheniramine 1–2 mg/cat PO q12–24h
Loratidine 0.5 mg/kg PO q24h
Cyproheptadine 1 mg/cat PO q12h
Diphenhydramine 2–4 mg/cat PO q8–12h
Hydroxyzine 5–10 mg/cat or 2.2 mg/kg PO q8–12h
Cetirizine 5 mg/cat PO q12h
+Antibiotics
! Doxycycline: effective against Mycoplasma spp., B. bronchiceptica, and C. felis, possible immunomodulatory effects ! Use caution when giving pills ! Follow with a meal or water via syringe
! Azithromycin: accumulates in tissues, may have immunomodulatory effects as well ! Typically dosed q72h after initial week ! Alternative dosing: daily for 30d.
! Pradofloxacin (JFMS 2008 10: 472-479): effective in cats with Mycoplasma spp., B. bronchiseptica, Staph. and Strep. Spp. ! Label limits dosing duration ! Esophageal stricture not an issue like doxycycline ! No difference when compared to amoxicillin
+Antibiotics
Reed, N. et al. Nasopharyngeal disease in Cats. JFMS (2012) 14, 317–326
+Altering local immunity
! 12-week old kittens (N=20)
! Treatment group (n=10) single, intranasal FVRC vaccine,
! Day 7 post-vaccination all kittens innoculated with B. bronchiseptica
! Measured effects were lost during the second 10 days of observation
6/30/16&
8&
+Altering local immunity
! Bottom line: Intranasal vaccination against FHV-1 and FCV confers cross-protection against challenge with an infectious agent (B. bronchiseptica) not contained in the vaccine
! Might provide protection against nonvaccinal organisms
! Nonspeci�c immunity likely becomes active while speci�c immunity develops " conferring protection more quickly
+Altering local immunity
Intron A (Schering Plough) 10,000 U/kg SQ q24h
Single dose feline Ultranasal FVRC
14 days
14 days
+Altering local immunity
! Based on the following: ! Interferon-�2b: interferons
are so-named for ability to interfere with viral replication
! Vaccination may strengthen local immunity (even against agents not included in the vaccine)
! In this study of 47 cats identified for inclusion ! 16 were excluded because
their signs resolved spontaneously (removal from the shelter)
! 4 excluded for severe ocular disease
! Results ! 13 cats that received the
human IFN-�2b, eight had a clinical score <3 by day 14 ! No SE noted, tolerated SQ
injections well ! All 14 cats given IN vaccine
improved clinical scores ! NB: No untreated control
group! ! PCR + FHV-1 or FCV 27.3%
and 36.4% of cats in group A and group B ! All PCR + cats improved
+Take home points…
! Reduce stress
! Supportive care: cleaning crusted debris from the eyes and nose, subcutaneous fluids, oral buprenorphine and topical ophthalmic antibiotics
! Treat pain! ! Almost 50% of those cats received buprenorphine
! Consider interferon or IN vaccination for chronic cats that fail to respond to traditional therapy
+Speaking of stress…
Preventive Veterinary Medicine 117 (2014) 266–275
+Effect of gentling on shelter cats
102 anxious cats at shelter admission
Measured: Daily mood and changes in mood over time
S-IgA via fecal ELISA Initial and follow-up PCR and bacterial culture
Development of URTD
10 Days
6/30/16&
9&
+Effect of gentling on shelter cats
! S-IgA was higher in Gentled than Control cats ! A significant increase over
days was found in both groups
! S-IgA values were greater for Gentled Content cats than Content Control cats
! S-IgA was significantly greater for positive than for negative responders to gentling
S-IgA via fecal ELISA
+Effect of gentling on shelter cats
! Mycoplasma felis isolated from 21% of cats at admission ! FHV, FCV, and B.
bronchiseptica 2% each
! Significant increase in shedding over time in non-gentled cats, but not gentled cats
! Control cats 2.37 times more likely to develop clinical URD over time than cats that received the Gentling treatment
Serial PCR, bacterial culture and URTD development
+Inhibiting viral replication
! Most promising orally is famciclovir ! Guanosine analogue
! Prodrug activated by viral thymidine kinase
! Interferes with viral DNA polymerase and DNA synthesis
! Most effective against herpesviruses ! Variable absorption in cats
! Ineffective for latent viruses
Antiviral drugs
+Inhibiting viral replication
! Several studies showing improvement in herpetic cats treated with topical eye drops (cidofovir) or oral famciclovir ! Various reported doses
! 62.5 mg/cat, 125 mg/cat, 40-90 mg/kg all q8h PO
! Reduce dose in renal insufficiency ! At high doses, acyclovir caused myelosuppression and renal
tubular necrosis and hepatic necrosis
+Inhibiting viral replication
! Thought to inhibit viral replication
! Variable results
! May help reduce reactivated shedding
! Tablets may help with ocular manifestation
! May contribute to worse outcome in shelters
! No significant reduction in in vitro replication
Lysine: it (maybe) won’t hurt them
+Conflicting studies on lysine
6/30/16&
10&
+Inhibiting viral replication
Veterinary Microbiology 177 (2015) 78–86
Adapted from emdmillipore.com
+Inhibiting viral replication
! Demonstrated successful inhibition of FCV using synthetic siRNAs in vitro
! Used laboratory-derived and fields strains of FCV
! Cells treated prophylactically rather than therapeutically
! Need more trials
+Inhibiting viral replication
! Leflunomide ! Inhibits pyrimidine
synthesis
! Used in the treatment of human HSV-1 immunosuppressed individual ! Thought to inhibit viron
assembly
! Kirk’s CVT – someone is using this!
+Other possible treatments: Maropitant
! Inhibits tissue binding of substance P via tachykinin receptor antagonism
! Tachykinins are released from mast cells during tissue injury with inflammation
! Blocking substance P at NK-1 receptors could reduce pain, inflammation, exudation, edema, allergic signs
+Other possible treatments: probiotic administration
! Use of Fortiflora (Enterococcus faecium SF68)
! 12 cats divided into treatment and control groups
! Lessened morbidity in group receiving SF68
! Pilot Study – none since then…
+Other possible treatments
! Increased ltranscription of IL-6, IL-10, IL-12 p40, IFN-�, in nasal biopsies with an inflammatory infiltrate compared with normal biopsies
! No alteration in gene transcription of Il-4, IL-5, IL-16, and IL-18.
! Indicates a predominant helper T cell (Th)1 response to inflammatory stimuli, which could lead to more targeted therapies to modify this inflammatory response.
! Other immunosuppressives
! Cyclosporine: binds to cyclophilin as a calcineurin inhibitor, inhibits IL-2 release by T cells
! Apoquel use in cats in the future
! Inhibits JAK1 and its related cytokines: IL-2, IL-4, IL-6, IL-13
6/30/16&
11&
+Other possible treatments
! Radiation therapy?
! Discussed at NAVC
! Previous clinical trial at NCSU
+Prevention A quick review of AAHA/AAFP guidelines
+Vaccination
! FHV-1: core vaccine ! Intranasal or injectable ! Protect against disease, do not
prevent infection or latency
! FCV: core vaccine ! Multivalent vaccines may offer
better protection against VS-FCV
! Intranasal or injectable ! Protect against disease, do not
prevent infection or latency
! B. bronchiseptica and C. felis not recommended as signs are generally self-limiting
+Vaccination: inactivated versus ML
! Two groups SPF kittens ! Group 1: FVRCP inactivated
SQ ! Group 2: FVRCP modified
live
! Measured Ab titers to agents weekly after first innoculation ! ML more likely to
seroconvert for FPV by day 7 (both groups seroconverted by day 14)
! FHV1 response more rapid with inactivated
+Vaccination: Considerations for VS-FCV
! Cats afflicted in previous outbreaks had been vaccinated
! Complicated relationship between variants ! “Strains” if more than 20% difference between two capsid
sequences
! Dual-strain vaccine contains traditional FCV and a VS-FCV strain ! Stimulates antibody production with testing against field strains
from Europe and previous VS-FCV strains
! Challenge with FS-VSC in dual-strain vaccinates resulted in reduced clinical signs
+The doctor is in…
! 15yo FS DSHA
! Chronic sneezing, nasal discharge, and labored breathing
! Signs worsened after being diagnosed with pancreatitis 6 months ago
! Chronic vomiting since the episode of pancreatitis along with hyporexia
! Other history: hyperthyroid treated with I-131 5 years ago, HCM diagnosed two years ago
6/30/16&
12&
+Considerations
! Chronic rhinitis
! Nasal tumor (Lymphoma)
! Dental disease
! Nasopharyngeal stenosis
+Back to Doctor
! Rhinscopy and biopsy ! Mixed L-P and neutrophilic